This invention relates to a process for preparing a protein fraction comprising proteins secreted by human cells. The secreted proteins inhibit growth of heterologous human cells. The invention also relates to the protein fraction which is a product of the process.
Numerous stimulators of cell growth are secreted by mammalian cells, but only a few substances capable of inhibiting cell growth are known. For example, interferon preparations reversibly inhibit multiplication of conspecific, homologous cells in cell culture. Paucker et al., Virology 17: 324 (1962), and Gresser et al., Nature 239: 167 (1972), report experiments in which these growth-inhibiting effects were observed. Apart from interferons, only a few proteins or protein mixtures with capacity to inhibit normal or neoplastic cell growth have been described.
For example, Redding et al., Proc. Natl. Acad. Sci. USA 79: 7014 (1982), describe isolation of a purified fraction from porcine hypothalami. This fraction displayed antimitogenic activity when introduced to growing cultures of certain normal and neoplastic cell lines. Loss of antimitogenic activity following exposure of the purified fraction to proteases indicated that the activity was probably associated with one or more polypeptides.
Kinders et al., Biochem. J. 190: 605 (1980), observed that certain glycopeptides isolated from cell surfaces of mouse cerebral cortex inhibited growth of baby hamster kidney cells. Burzynski et al., Physiol. Chem. Phys. 8: 13 (1976), isolated medium-sized peptides from human urine which inhibited DNA synthesis and mitosis in certain human neoplastic cell lines.
Sloane, U.S. Pat. No. 4,359,415, discloses a process for preparing a glycoprotein fraction from human urine containing a glycoprotein exhibiting antineoplastic activity.
Holley et al., Proc. Natl. Acad. Sci. USA 77: 5989 (1980), describe isolation of two high molecular weight growth inhibitors from cultures of monkey epithelial kidney cells. These substances selectively and reversibly inhibited growth of the cells from which they were derived.
McMahon et al., Proc. Natl. Acad. Sci. USA 79: 456 (1982), disclose purification of an inhibitor of cell proliferation from cultures of nonmalignant rat hepatic epithelial cells. This substance, which was determined to have a molecular weight of approximately 26,000 daltons, inhibited growth of nonmalignant rat liver cells in culture, but did not affect growth of malignant rat liver cells.
Endogenous substances capable of inhibiting growth of mammalian cells are of interest as potential therapeutic agents.